MiR-19a-3p regulates the Forkhead box F2-mediated Wnt/β-catenin signaling pathway and affects the biological functions of colorectal cancer cells.
Colorectal cancer (CRC) is one of the most common malignancies worldwide.
To explore the expression of microRNA miR-19a-3p and Forkhead box F2 (FOXF2) in patients with CRC and the relevant mechanisms.
Sixty-two CRC patients admitted to the hospital were enrolled into the study group, and sixty healthy people from the same period were assigned to the control group. Elbow venous blood was sampled from the patients and healthy individuals, and blood serum was saved for later analysis. MiR-19a-3p mimics, miR-19a-3p inhibitor, miR-negative control, small interfering-FOXF2, and short hairpin-FOXF2 were transfected into HT29 and HCT116 cells. Then quantitative polymerase chain reaction was performed to quantify the expression of miR-19a-3p and FOXF2 in HT29 and HCT116 cells, and western blot (WB) analysis was conducted to evaluate the levels of FOXF2, glycogen synthase kinase 3 beta (GSK-3β), phosphorylated GSK-3β (p-GSK-3β), β-catenin, p-β-catenin, α-catenin, N-cadherin, E-cadherin, and vimentin. The MTT, Transwell, and wound healing assays were applied to analyze cell proliferation, invasion, and migration, respectively, and the dual luciferase reporter assay was used to determine the correlation of miR-19a-3p with FOXF2.
The patients showed high serum levels of miR-19a-3p and low levels of FOXF2, and the area under the curves of miR-19a-3p and FOXF2 were larger than 0.8. MiR-19a-3p and FOXF2 were related to sex, tumor size, age, tumor-node-metastasis staging, lymph node metastasis, and differentiation of CRC patients. Silencing of miR-19a-3p and overexpression of FOXF2 suppressed the epithelial-mesenchymal transition, invasion, migration, and proliferation of cells. WB analysis revealed that silencing of miR-19a-3p and FOXF2 overexpression significantly suppressed the expression of p-GSK-3β, β-catenin, N-cadherin, and vimentin; and increased the levels of GSK-3β, p-β-catenin, α-catenin, and E-cadherin. The dual luciferase reporter assay confirmed that there was a targeted correlation of miR-19a-3p with FOXF2. In addition, a rescue experiment revealed that there were no differences in cell proliferation, invasion, and migration in HT29 and HCT116 cells co-transfected with miR-19a-3p-mimics+sh-FOXF2 and miR-19a-3p-inhibitor+si-FOXF2 compared to the miR-negative control group.
Inhibiting miR-19a-3p expression can upregulate the FOXF2-mediated Wnt/β-catenin signaling pathway, thereby affecting the epithelial-mesenchymal transition, proliferation, invasion, and migration of cells. Thus, miR-19a-3p is likely to be a therapeutic target in CRC.
Yu FB
，Sheng J
，Yu JM
，Liu JH
，Qin XX
，Mou B
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COL4A1, negatively regulated by XPD and miR-29a-3p, promotes cell proliferation, migration, invasion and epithelial-mesenchymal transition in liver cancer cells.
Collagen type IV alpha 1 (COL4A1) exerts tumor-promoting functions in several tumors. However, its role in liver cancer remains not fully understood. Hence, this study aims to investigate the role of COL4A1 in regulating liver cancer cell behaviors and to validate its upstream regulatory mechanism.
Expression of xeroderma pigmentosum D (XPD) and COL4A1 was examined by qRT-PCR and western blot. Cell proliferation, migration, and invasion were evaluated. The protein levels of N-cadherin, vimentin, and E-cadherin were determined by western blot to evaluate epithelial-mesenchymal transition (EMT). The interaction between miR-29a-3p and COL4A1 was analyzed by luciferase reporter assay.
COL4A1 overexpression significantly promoted cell proliferation, migration, invasion, and EMT in Hep3B cells. In contrast, COL4A1 silencing yielded the opposite effects in HepG2 cells. Expression of COL4A1 was increased, whereas expression of XPD and miR-29a-3p was decreased in HCC tissues compared to controls. COL4A1 mRNA level was negatively correlated with expression of XPD and miR-29a-3p in HCC tissues. Furthermore, XPD silencing-mediated up-regulation of COL4A1 expression was attenuated by miR-29a-3p mimic. Moreover, miR-29a-3p mimic inhibited Hep3B cell proliferation, migration, and invasion by directly targeting COL4A1.
COL4A1 is negatively regulated by XPD-miR-29a-3p axis and promotes liver cancer progression in vitro.
Zhang H
，Wang Y
，Ding H
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Upregulation of microRNA-140-3p inhibits epithelial-mesenchymal transition, invasion, and metastasis of hepatocellular carcinoma through inactivation of the MAPK signaling pathway by targeting GRN.
Invasion and metastasis in hepatocellular carcinoma (HCC) results in poor prognosis. Human intervention in these pathological processes may benefit the treatment of HCC. The aim of the present study is to elucidate the mechanism of miR-140-3p affecting epithelial-mesenchymal transition (EMT), invasion, and metastasis in HCC. Microarray analysis was performed for differentially expressed genes screening. The target relationship between miR-140-3p and GRN was analyzed. Small interfering RNA (siRNA) against granulin (GRN) was synthesized. EMT markers were detected, and invasion and migration were evaluated in HCC cells introduced with a miR-140-3p inhibitor or mimic, or siRNA against GRN. A mechanistic investigation was conducted for the determination of mitogen-activated protein kinase (MAPK) signaling pathway-related genes and EMT markers (E-cadherin, N-cadherin, and Vimentin). GRN was highlighted as an upregulated gene in HCC. GRN was a target gene of miR-140-3p. Elevation of miR-140-3p or inhibition of GRN restrained the EMT process and suppressed the HCC cell migration and invasion. HCC cells treated with the miR-140-3p mimic or siRNA-GRN exhibited decreased GRN expression and downregulated the expressions of the MAPK signaling pathway-related genes, N-cadherin, and Vimentin but upregulated the expression of E-cadherin. GRN silencing can reverse the activation of the MAPK signaling pathway and induction of EMT mediated by miR-140-3p inhibition. Taken together, the results show that miR-140-3p confers suppression of the MAPK signaling pathway by targeting GRN, thus inhibiting EMT, invasion, and metastasis in HCC.
Zhang QY
，Men CJ
，Ding XW
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ResearchGate
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钛学术
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